PubMed:21383697
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/21383697","sourcedb":"PubMed","sourceid":"21383697","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/21383697","text":"MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways.\nThe tyrosine kinase c-Src is upregulated in various human cancers, but the molecular mechanisms underlying c-Src-mediated tumor growth remain unclear. Here we examined the involvement of microRNAs in the c-Src-mediated tumor growth. Microarray profiling revealed that c-Src activation downregulates a limited set of microRNAs, including miR-99a, which targets oncogenic mammalian target of rapamycin (mTOR) and fibroblast growth factor receptor 3 (FGFR3). Re-expression of miR-99a suppressed tumor growth of c-Src-transformed cells, and this effect was restored by the overexpression of mTOR. The downregulation of miR-99a was also observed in epidermal growth factor- and Ras-transformed cells, and it was suppressed by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Furthermore, miR-99a downregulation is associated with mTOR/FGFR3 upregulation in various human lung cancer cells/tissues. The tumorigenicity of these cells was suppressed by the introduction of miR-99a. These findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways.","tracks":[{"project":"Allie","denotations":[{"id":"SS1_21383697_3_0","span":{"begin":482,"end":511},"obj":"expanded"},{"id":"SS2_21383697_3_0","span":{"begin":513,"end":517},"obj":"abbr"},{"id":"SS1_21383697_3_1","span":{"begin":523,"end":558},"obj":"expanded"},{"id":"SS2_21383697_3_1","span":{"begin":560,"end":565},"obj":"abbr"},{"id":"SS1_21383697_5_0","span":{"begin":848,"end":880},"obj":"expanded"},{"id":"SS2_21383697_5_0","span":{"begin":882,"end":886},"obj":"abbr"}],"relations":[{"id":"AE1_21383697_3_0","pred":"abbreviatedTo","subj":"SS1_21383697_3_0","obj":"SS2_21383697_3_0"},{"id":"AE1_21383697_3_1","pred":"abbreviatedTo","subj":"SS1_21383697_3_1","obj":"SS2_21383697_3_1"},{"id":"AE1_21383697_5_0","pred":"abbreviatedTo","subj":"SS1_21383697_5_0","obj":"SS2_21383697_5_0"}],"attributes":[{"subj":"SS1_21383697_3_0","pred":"source","obj":"Allie"},{"subj":"SS2_21383697_3_0","pred":"source","obj":"Allie"},{"subj":"SS1_21383697_3_1","pred":"source","obj":"Allie"},{"subj":"SS2_21383697_3_1","pred":"source","obj":"Allie"},{"subj":"SS1_21383697_5_0","pred":"source","obj":"Allie"},{"subj":"SS2_21383697_5_0","pred":"source","obj":"Allie"}]},{"project":"performance-test","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":1011,"end":1018},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":993,"end":997},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"performance-test"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"performance-test"}]},{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":170,"end":177},"obj":"HP_0002664"},{"id":"T2","span":{"begin":234,"end":239},"obj":"HP_0002664"},{"id":"T3","span":{"begin":331,"end":336},"obj":"HP_0002664"},{"id":"T4","span":{"begin":604,"end":609},"obj":"HP_0002664"},{"id":"T5","span":{"begin":993,"end":1004},"obj":"HP_0100526"},{"id":"T6","span":{"begin":998,"end":1004},"obj":"HP_0002664"},{"id":"T7","span":{"begin":1187,"end":1192},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1225,"end":1232},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"},{"subj":"T7","pred":"source","obj":"PubmedHPO"},{"subj":"T8","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":957,"end":962},"obj":"gene:2261"},{"id":"T1","span":{"begin":993,"end":1004},"obj":"disease:C0242379"},{"id":"T2","span":{"begin":957,"end":962},"obj":"gene:2261"},{"id":"T3","span":{"begin":993,"end":1004},"obj":"disease:C0684249"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"sentences","denotations":[{"id":"TextSentencer_T1","span":{"begin":0,"end":111},"obj":"Sentence"},{"id":"TextSentencer_T2","span":{"begin":112,"end":262},"obj":"Sentence"},{"id":"TextSentencer_T3","span":{"begin":263,"end":344},"obj":"Sentence"},{"id":"TextSentencer_T4","span":{"begin":345,"end":567},"obj":"Sentence"},{"id":"TextSentencer_T5","span":{"begin":568,"end":704},"obj":"Sentence"},{"id":"TextSentencer_T6","span":{"begin":705,"end":896},"obj":"Sentence"},{"id":"TextSentencer_T7","span":{"begin":897,"end":1019},"obj":"Sentence"},{"id":"TextSentencer_T8","span":{"begin":1020,"end":1100},"obj":"Sentence"},{"id":"TextSentencer_T9","span":{"begin":1101,"end":1296},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":111},"obj":"Sentence"},{"id":"T2","span":{"begin":112,"end":262},"obj":"Sentence"},{"id":"T3","span":{"begin":263,"end":344},"obj":"Sentence"},{"id":"T4","span":{"begin":345,"end":567},"obj":"Sentence"},{"id":"T5","span":{"begin":568,"end":704},"obj":"Sentence"},{"id":"T6","span":{"begin":705,"end":896},"obj":"Sentence"},{"id":"T7","span":{"begin":897,"end":1019},"obj":"Sentence"},{"id":"T8","span":{"begin":1020,"end":1100},"obj":"Sentence"},{"id":"T9","span":{"begin":1101,"end":1296},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"attributes":[{"subj":"TextSentencer_T1","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T2","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T3","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T4","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T5","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T6","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T7","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T8","pred":"source","obj":"sentences"},{"subj":"TextSentencer_T9","pred":"source","obj":"sentences"},{"subj":"T1","pred":"source","obj":"sentences"},{"subj":"T2","pred":"source","obj":"sentences"},{"subj":"T3","pred":"source","obj":"sentences"},{"subj":"T4","pred":"source","obj":"sentences"},{"subj":"T5","pred":"source","obj":"sentences"},{"subj":"T6","pred":"source","obj":"sentences"},{"subj":"T7","pred":"source","obj":"sentences"},{"subj":"T8","pred":"source","obj":"sentences"},{"subj":"T9","pred":"source","obj":"sentences"}]},{"project":"UBERON-AE","denotations":[{"id":"PD-UBERON-AE-B_T1","span":{"begin":993,"end":997},"obj":"http://purl.obolibrary.org/obo/UBERON_0002048"},{"id":"PD-UBERON-AE-B_T2","span":{"begin":1011,"end":1018},"obj":"http://purl.obolibrary.org/obo/UBERON_0000479"}],"attributes":[{"subj":"PD-UBERON-AE-B_T1","pred":"source","obj":"UBERON-AE"},{"subj":"PD-UBERON-AE-B_T2","pred":"source","obj":"UBERON-AE"}]},{"project":"DisGeNet-2017-sample","denotations":[{"id":"T350","span":{"begin":910,"end":917},"obj":"gene:407055"},{"id":"T351","span":{"begin":993,"end":1004},"obj":"disease:C0242379"},{"id":"T352","span":{"begin":957,"end":962},"obj":"gene:2261"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T350","obj":"T351"},{"id":"R2","pred":"associated_with","subj":"T350","obj":"T351"},{"id":"R3","pred":"associated_with","subj":"T350","obj":"T351"},{"id":"R4","pred":"associated_with","subj":"T352","obj":"T351"},{"id":"R5","pred":"associated_with","subj":"T352","obj":"T351"},{"id":"R6","pred":"associated_with","subj":"T352","obj":"T351"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T350","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T351","pred":"source","obj":"DisGeNet-2017-sample"},{"subj":"T352","pred":"source","obj":"DisGeNet-2017-sample"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"21383697-6#13#20#gene407055","span":{"begin":910,"end":917},"obj":"gene407055"},{"id":"21383697-6#60#65#gene2261","span":{"begin":957,"end":962},"obj":"gene2261"},{"id":"21383697-6#96#107#diseaseC0242379","span":{"begin":993,"end":1004},"obj":"diseaseC0242379"},{"id":"21383697-6#96#107#diseaseC0684249","span":{"begin":993,"end":1004},"obj":"diseaseC0684249"},{"id":"21383697-6#96#107#diseaseC1306460","span":{"begin":993,"end":1004},"obj":"diseaseC1306460"},{"id":"21383697-6#96#107#diseaseC0242379","span":{"begin":993,"end":1004},"obj":"diseaseC0242379"},{"id":"21383697-6#96#107#diseaseC0684249","span":{"begin":993,"end":1004},"obj":"diseaseC0684249"},{"id":"21383697-6#96#107#diseaseC1306460","span":{"begin":993,"end":1004},"obj":"diseaseC1306460"}],"relations":[{"id":"13#20#gene40705596#107#diseaseC0242379","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC0242379"},{"id":"13#20#gene40705596#107#diseaseC0684249","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC0684249"},{"id":"13#20#gene40705596#107#diseaseC1306460","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC1306460"},{"id":"13#20#gene40705596#107#diseaseC0242379","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC0242379"},{"id":"13#20#gene40705596#107#diseaseC0684249","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC0684249"},{"id":"13#20#gene40705596#107#diseaseC1306460","pred":"associated_with","subj":"21383697-6#13#20#gene407055","obj":"21383697-6#96#107#diseaseC1306460"},{"id":"60#65#gene226196#107#diseaseC0242379","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC0242379"},{"id":"60#65#gene226196#107#diseaseC0684249","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC0684249"},{"id":"60#65#gene226196#107#diseaseC1306460","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC1306460"},{"id":"60#65#gene226196#107#diseaseC0242379","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC0242379"},{"id":"60#65#gene226196#107#diseaseC0684249","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC0684249"},{"id":"60#65#gene226196#107#diseaseC1306460","pred":"associated_with","subj":"21383697-6#60#65#gene2261","obj":"21383697-6#96#107#diseaseC1306460"}],"attributes":[{"subj":"21383697-6#13#20#gene407055","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#60#65#gene2261","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC0242379","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC0684249","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC1306460","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC0242379","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC0684249","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"21383697-6#96#107#diseaseC1306460","pred":"source","obj":"DisGeNET5_gene_disease"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Allie","color":"#eccf93","default":true},{"id":"performance-test","color":"#b593ec"},{"id":"PubmedHPO","color":"#93ec9b"},{"id":"DisGeNET","color":"#ec93a4"},{"id":"sentences","color":"#93beec"},{"id":"UBERON-AE","color":"#d8ec93"},{"id":"DisGeNet-2017-sample","color":"#e593ec"},{"id":"DisGeNET5_gene_disease","color":"#93eccb"}]}]}}